Transport, separation and characterization of micro- or nano-scale particles has a wide variety of applications ranging from industrial applications, to biological applications, to environmental applications. For example, in the field of biology, the separation of cells has numerous applications in medicine and biotechnology. Historically, sorting technologies focused on gross physical characteristics, such as particle size or density, or utilized some affinity interaction, such as receptor-ligand interactions or reactions with immunologic targets.
Electromagnetic response properties of materials have been utilized for particle sorting and characterization. For example, dielectrophoretic separators utilize non-uniform DC or AC electric fields for separation of particles. See, e.g., U.S. Pat. No. 5,814,200, Pethig et al., entitled “Apparatus for Separating By Dielectrophoresis.”
Coherent light has been used to trap and manipulate particles. One of the earliest workers in the field was Ashkin, U.S. Pat. No. 3,808,550 entitled “Apparatuses for Trapping and Accelerating Neutral Particles” which disclosed systems for trapping or containing particles through radiation pressure. Lasers generating coherent optical radiation were the preferred source of optical pressure.
Other particle manipulation techniques include the use of atomic force microscopy (AFM) or magnetic force microscopy (MFM). An AFM uses a cantilever, sometimes with a receptor attached to the cantilever tip, to identify and manipulate a single cell or protein on a surface by stretching the cell in an out-of-plane direction. Similarly, an MFM utilizes a magnetic field to manipulate and stretch a cell or protein with a magnetic bead attached thereto in an out-of-plane direction.
The sorting of individual cells or micro- or nano-scale particles is an old problem, whether attempting to isolate a single cell or particle, or identifying a specific sub-population of cells or particles that behave differently or have different properties than the rest of the population. While instruments and techniques exist to enable cells or particles to be seen, manipulation of single cells or particles, or groups of them within a larger population, has been problematic.
As noted above, one traditional method of cell manipulation involves laser capture in which cells can be trapped using a laser beam. However, such systems are slow, laser power intensive, and cannot be automated to isolate and manipulate multiple cells. Another traditional method, atomic force microscopy, can be used to identify and manipulate a single cell. However, again, the instrumentation cannot be automated to isolate and manipulate multiple cells. The use of magnetic tweezers has also been tried. However, that technique produces an out-of-plane pulling force on a cell and cannot be automated to isolate and manipulate multiple cells.
Accordingly, the need still exists for a technique which can isolate and trap individuals cells or micro- or nano-scale particles, and then readily manipulate the cells/particles for transport and testing or to separate them from a heterogeneous population. Desirably, such a technique would be able to manipulate thousands or tens of thousands of individual cells or particles in a short period of time.